Approach to the Patient with ANEMIA

1. Approach to the Patient with ANEMIA Lisa Mohr, MD Mike Tuggy, MD

2. Objectives • Review basic science of the RBC • Define Anemia • Review key aspects of history, physical and lab evaluation • Review a systematic approach to the differential diagnosis • Case-based application of clinical concepts

3. RBC-The important players • Hemoglobin • reversibly binds and transports 02 from lungs to tissues • 4 globin chains & iron

4. RBC-The important players (2) • Iron • key element in the production of hemoglobin • absorption is poor • Transferrin • iron transporter • Ferritin • iron binder, measure of iron stores, *also acute phase reactant*

5. Definitions • Anemia-values of hemoglobin, hematocrit or RBC counts which are more than 2 standard deviations below the mean • HGB<13.5 g/dL (men) <12 (women) • HCT<41% (men) <36 (women)

6. CASE • ML is a 64-year old male who has not had any primary care for several years. When he tried to give blood last week, he was told that he was anemic. He presents to your clinic for evaluation. • What would you do??

7. Evaluation of the Patient • HISTORY • Is the patient bleeding? • Actively? In past? • Is there evidence for increased RBC destruction? • Is the bone marrow suppressed? • Is the patient nutritionally deficient? Pica? • PMH including medication review, toxin exposure

8. Evaluation of the Patient (2) REVIW OF SYMPTOMS • Decreased oxygen delivery to tissues • Exertional dyspnea • Dyspnea at rest • Fatigue • Signs and symptoms of hyperdynamic state • Bounding pulses • Palpitations • Life threatening: heart failure, angina, myocardial infarction • Hypovolemia • Fatiguablitiy, postural dizziness, lethargy, hypotension, shock and death

9. Evaluation of the Patient (3) PHYSICAL EXAM •Stable or Unstable? -ABCs -Vitals •Pallor •Jaundice -hemolysis •Lymphadenopathy •Hepatosplenomegally •Bony Pain •Petechiae •Rectal-? Occult blood

10. Laboratory Evaluation • Initial Testing • CBC w/ differential (includes RBC indices) • Reticulocyte count • Peripheral blood smear

11. Laboratory Evaluation (2) • Bleeding • Serial HCT or HGB • Iron Deficiency • Iron Studies • Hemolysis • Serum LDH, indirect bilirubin, haptoglobin, coombs, coagulation studies • Bone Marrow Examination • Others-directed by clinical indication • hemoglobin electrophoresis • B12/folate levels

12. Differential Diagnosis • Classification by Pathophysiology • Blood Loss • Decreased Production • Increased Destruction • Classification by Morphology • Normocytic • Microcytic • Macrocytic

13. Blood Loss • Acute • Traumatic • Variety of sources • Melena, hematemesis, menometrorrhagia • Chronic • Occult bleeding • Colonic polyp/carcinonma

14. Decreased Production • Infectious • Neoplastic • Endocrine • Nutritional Deficiency • Anemia of Chronic Disease

15. Decreased ProductionINFECTIOUS • Bacterial • Tuberculosis • MAI • Viral • HIV • Parvovirus

16. Decreased ProductionNEOPLASTIC • Leukemia • Lymphoma/Myeloma • Myeloproliferative Syndromes • Myelodysplasia

17. Decreased ProductionENDOCRINE • Thyroid Dysfunction • Hypothyroidism • Erythropoietin Deficiency • Renal Failure

18. Decreased ProductionNUTRITIONAL DEFICIENCY • Iron • B12 • Folate

19. Macrocytic Anemia • MCV > 100 • Megaloblastic:Abnormalities in nucleic acid metabolism • B12, Folate • Non-megaloblastic:Abnormal RBC maturation • Myelodysplasia • ETOH, liver dz, hypothryroidism, chemotherapy/drugs

20. Microcytic Anemia • MCV <80 • Reduced iron availability • Reduced heme synthesis • Reduced globin production

21. Microcytic AnemiaREDUCED IRON AVAILABILTY • Iron Deficiency • Deficient Diet/Absorption • Increased Requirements • Blood Loss • Iron Sequestration • Anemia of Chronic Disease • Low serum iron, low TIBC, normal serum ferritin • MANY!! • Chronic infection, inflammation, cancer, liver disease

22. Microcytic AnemiaREDUCED HEME SYNTHESIS • Lead poisoning • Acquired or congenital sideroblastic anemia • Characteristic smear finding: Basophylic stippling

23. Microcytic AnemiaREDUCED GLOBIN PRODUCTION • Thalassemias • Smear Characteristics • Hypochromia • Microcytosis • Target Cells • Tear Drops

24. Lab tests of iron deficiency of increased severity

25. Differential Diagnosis-Revisited • Classification by Pathophysiology • Blood Loss • Decreased Production • Increased Destruction

26. INCREASED DESTRUCTION • Immune Mediated • Non-immune Mediated

27. Increased DestructionIMMUNE MEDIATED • Cold Agglutinin • Paroxysmal nocturnal hemoglobinuria • Post mycoplasmal hemolytic anemia • Warm Agglutinin • Drug induced • Autoimmune hemolytic anemia • Transfusion reaction

28. Increased DestructionNON-IMMUNE MEDIATED • Extra-corpuscular • Macro-circulatory • Hypersplenism • Extracorporeal circulation • Micro-circulatory • DIC • TTP • HUS • Intra-corpuscular • RBC Wall (membrane or enzyme defects) • Heme or globin abnormalities (HbS, C)

29. Back to M.L.-You appropriately decide to obtain more history! • HPI: “I’ve been a little more tired than usual, but I’ve been busy at work. I’m getting close to retirement. Nothing else is unusual. I avoid doctors if I can” • PMH: Inguinal hernia repair 20 yrs ago • FH: F & MGF-heart attack(age 80), brother-alcoholism • SH: Married x44yr, smokes 1ppd, “a couple beers/night” • MEDS: daily multivitamin • ALLERGIES: none • ROS:+fatigue, +urine seems a little darker lately

30. More on M.L. • P.E. findings • T 98.4 HR 98 Resp 20 BP 112/70 • Gen: NAD, appears younger than stated age • HEENT: skin and conjunctiva slightly pale • NECK: no adenopathy or thyromegally • Chest: CTAB • CV: RRR, no murmur • ABD: no HSM, soft, normoactive bowel sounds • GU: normal male • Rectal: no masses, prostate smooth/not enlarged, guaiac negative stool

31. M.L.’s Initial Labs • Only a CBC w/ diff was obtained: • WBC: 8.2, HCT 32.2, MCV 79, Platelets 221, differential - normal

32. Initial Thoughts? • Blood loss? • Age places him at risk for colon CA • Decreased Production? • Alcohol use, Iron deficiency • Increased Destruction? • “Darker urine” lately

33. Further Work-up • CAGE questions • Peripheral Blood Smear • Reticulocyte count • Iron Studies • Ferritin • TIBC • % Saturation • Urinalysis • FOBT or colonoscopy referal

34. More Results • CAGE screen reveals no positive responses • Smear reveals microcytic, microchromic RBCs • Retic count is interpreted as “low” • Urinalysis negative for hemoglobin • FOBT: not completed by patient • Iron Studies • Ferritin: 10 • TIBC: 350 • % Sat: 15

35. What’s next? • Rule out Sources of Bleeding • Counseling regarding colon CA and referral for colonoscopy • Consider oral iron therapy • Dietary counseling (iron sources, limiting etoh, etc) • Encourage follow-up for health care maintenance • Vaccinations (Tetnus/pneumovax) • Other cancer screening • Cholesterol Screen

36. Diagnosis • Colonoscopy revealed small suspicious lesion in sigmoid colon, pathology revealing adenocarcinoma. – Excised surgically, no mets. • Routine labs, one year later, reveal an HCT of 40%. He feels “better than ever”!

37. References • Schrier, Stanley.Approach to the patient with anemia. Up to Date. 2004 • Schrier, Stanley. Anemia of Chronic Disease. Up to Date. 2004 • Schrier, Stanley. Anemias due to decreased red Cell Production. Up to Date 2004 • Schrier, Stanley. Causes and diagnosis of anemia due to iron deficiency. Up to Date. 2004 • Tierney, et al. Anemias. Current Medical Diagnosis and treatment. 2003. Pp469-489